1LG1: Crystal Structure Of Human Chitotriosidase In Complex With Chitobiose

Citation:
Abstract
Chitin hydrolases have been identified in a variety of organisms ranging from bacteria to eukaryotes. They have been proposed to be possible targets for the design of novel chemotherapeutics against human pathogens such as fungi and protozoan parasites as mammals were not thought to possess chitin-processing enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher disease with plasma levels of the enzyme elevated up to 2 orders of magnitude. The chitotriosidase was shown to be active against colloidal chitin and is inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal structure of the human chitotriosidase and complexes with a chitooligosaccharide and allosamidin are described. The structures reveal an elongated active site cleft, compatible with the binding of long chitin polymers, and explain the inactivation of the enzyme through an inherited genetic deficiency. Comparison with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian lectins by the mutation of key residues in the active site, tuning the substrate binding specificity. The soaking experiments with allosamidin and chitooligosaccharides give insight into ligand binding properties and allow the evaluation of differential binding and design of species-selective chitinase inhibitors.
PDB ID: 1LG1Download
MMDB ID: 20647
PDB Deposition Date: 2002/4/14
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.78  Å
Source Organism:
Similar Structures:
Biological Unit for 1LG1: monomeric; determined by author
Molecular Components in 1LG1
Label Count Molecule
Protein (1 molecule)
1
Chitotriosidase(Gene symbol: CHIT1)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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